Penn surgeons connected a pig liver to the body of a deceased person, showing it could work for living patients

Penn Medicine surgeons announced Thursday they had successfully connected a functioning pig liver to the body of a recently deceased person, a pivotal test case for someday performing the procedure to help living patients.

The surgeons used a pig liver that had been genetically modified with the precision gene-editing technique called CRISPR, a key step that prevented the organ from being rejected by the person’s immune system.

The recipient had been declared “brain-dead,” meaning they had experienced a permanent loss of brain function, said Abraham Shaked, the lead surgeon on the project at the Penn Transplant Institute. But because a ventilator was still circulating oxygen throughout the person’s body, it was considered a valid proving ground for what it would be like to connect a pig liver to a living patient.

“It was amazing,” he said, describing the animal’s liver after it was connected. “It was functioning.”

Elsewhere, other surgeons have successfully transplanted pig hearts into two gravely ill human patients, extending their lives by a month or two. For now, Shaked and his colleagues have stopped short of doing that with pig livers, a far more complicated organ than the heart. Instead, the initial proof-of-concept procedure, performed in late December, involved connecting the pig liver to the person’s circulatory system through an external machine.

Yet it was nevertheless a significant advance, others not involved with the project said. Even this intermediate step — connecting a pig liver to a patient through an external machine — could serve as a “bridge” to recovery, said Jayme Locke, director of the transplant center at the University of Alabama at Birmingham.

The external pig liver could buy some time for gravely ill patients, keeping them alive until a human donor organ becomes available or until the patient’s own liver has a chance to recover, she said.

“This was the first step, and I think this was really valuable and important,” she said of the Penn study. “You can think of what they did as like dialysis for the liver.”

The pig was raised in a secure facility by eGenesis, a Cambridge, Mass.-based biotech firm which funded the study. Company scientists had edited the animal’s genome in 69 places so that the liver would be compatible with the human body. Some of the edits were designed to prevent rejection by the human immune system. Other edits eliminated the risk from viral DNA that is contained within the pig genome, company chief executive officer Mike Curtis said.

What’s more, the animal was a special breed, called a Yucatan mini pig, that grows to just 150 pounds — just big enough so that its organs are comparable in scale to their human counterparts.

Meanwhile in Philadelphia, the nonprofit Gift of Life Donor Program was on the alert for any families of deceased patients who might consent to donate the body for this type of research.

Program coordinators identified such a family in December, and a team from Penn then drove to Massachusetts to retrieve the pig liver from the eGenesis facility.

The liver’s function was maintained during the return journey by connecting it to a machine made by OrganOx, a company based in Oxford, England.

After connecting the pig liver to the deceased person’s circulatory system, the Penn team monitored the organ for three days and detected no signs of inflammation or other problems.

Transplant surgeons hope that eventually, livers and other organs from genetically modified pigs will provide at least a partial answer to the nation’s chronic shortage of donated human organs.

In 2023, even as the number of liver transplants passed 10,000 for the first time, many patients still were left waiting. More than 900 people died while waiting for a liver transplant, and close to 1,000 patients were removed from the waiting list because they became too sick for a transplant, according to the United Network for Organ Sharing (UNOS).

The Penn team now plans to repeat the pig-liver procedure with additional donors, measuring how well a pig liver filters toxins from the human bloodstream, Shaked said.

That will involve getting the consent of additional families who have lost their loved ones, said Rick Hasz, the president and chief executive officer of Gift of Life.

In such cases, surgeons must first determine whether the person’s organs can be immediately used for transplant, he said.

But when they are not, as in the December case at Penn, the deceased person still can play a broader role in the pursuit of science, Hasz said.

“It’s really a unique opportunity to still advance the science of transplantation and have a huge impact on helping not only one patient or two patients or three or four, like most organ donors can do,” he said. “It really can change the course of how we treat end-stage liver failure.”